F18-FDG PET/CT imaging early predicts pathologic complete response to induction chemoimmunotherapy of locally advanced head and neck cancer: preliminary single-center analysis of the checkrad-cd8 trial.

AIM: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy. METHODS: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3-14 days before (pre-ICIT) and 21-28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu). RESULTS: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value. CONCLUSION: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value. TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT03426657.

Three-dimensional Monte Carlo-based voxel-wise tumor dosimetry in patients with neuroendocrine tumors who underwent 177Lu-DOTATOC therapy.

BACKGROUND: Patients with advanced neuroendocrine tumors (NETs) of the midgut are suitable candidates for 177Lu-DOTATOC therapy. Integrated SPECT/CT systems have the potential to help improve the accuracy of patient-specific tumor dosimetry. Dose estimations to target organs are generally performed using the Medical Internal Radiation Dose scheme. We present a novel Monte Carlo-based voxel-wise dosimetry approach to determine organ- and tumor-specific total tumor doses (TTD). METHODS: A cohort of 14 patients with histologically confirmed metastasized NETs of the midgut (11 men, 3 women, 62.3 ± 11.0 years of age) underwent a total of 39 cycles of 177Lu-DOTATOC therapy (mean 2.8 cycles, SD ± 1 cycle). After the first cycle of therapy, regions of interest were defined manually on the SPECT/CT images for the kidneys, the spleen, and all 198 tracer-positive tumor lesions in the field of view. Four SPECT images, taken at 4 h, 24 h, 48 h and 72 h after injection of the radiopharmaceutical, were used to determine their effective half-lives in the structures of interest. The absorbed doses were calculated by a three-dimensional dosimetry method based on Monte Carlo simulations. TTD was calculated as the sum of all products of single tumor doses with single tumor volumes divided by the sum of all tumor volumes. RESULTS: The average dose values per cycle were 3.41 ± 1.28 Gy (1.91-6.22 Gy) for the kidneys, 4.40 ± 2.90 Gy (1.14-11.22 Gy) for the spleen, and 9.70 ± 8.96 Gy (1.47-39.49 Gy) for all 177Lu-DOTATOC-positive tumor lesions. Low- and intermediate-grade tumors (G 1-2) absorbed a higher TTD compared to high-grade tumors (G 3) (signed-rank test, p = < 0.05). The pre-therapeutic chromogranin A (CgA) value and the TTD correlated significantly (Pearson correlation: = 0.67, p = 0.01). Higher TTD resulted in a significant decrease of CgA after therapy. CONCLUSION: These results suggest that Monte Carlo-based voxel-wise dosimetry is a very promising tool for predicting the absorbed TTD based on histological and clinical parameters.

A deep learning approach to radiation dose estimation.

Currently methods for predicting absorbed dose after administering a radiopharmaceutical are rather crude in daily clinical practice. Most importantly, individual tissue density distributions as well as local variations of the concentration of the radiopharmaceutical are commonly neglected. The current study proposes machine learning techniques like Green's function-based empirical mode decomposition and deep learning methods on U-net architectures in conjunction with soft tissue kernel Monte Carlo (MC) simulations to overcome current limitations in precision and reliability of dose estimations for clinical dosimetric applications. We present a hybrid method (DNN-EMD) based on deep neural networks (DNN) in combination with empirical mode decomposition (EMD) techniques. The algorithm receives x-ray computed tomography (CT) tissue density maps and dose maps, estimated according to the MIRD protocol, i.e. employing whole organ S-values and related time-integrated activities (TIAs), and from measured SPECT distributions of 177Lu radionuclei, and learns to predict individual absorbed dose distributions. In a second step, density maps are replaced by their intrinsic modes as deduced from an EMD analysis. The system is trained using individual full MC simulation results as reference. Data from a patient cohort of 26 subjects are reported in this study. The proposed methods were validated employing a leave-one-out cross-validation technique. Deviations of estimated dose from corresponding MC results corroborate a superior performance of the newly proposed hybrid DNN-EMD method compared to its related MIRD DVK dose calculation. Not only are the mean deviations much smaller with the new method, but also the related variances are much reduced. If intrinsic modes of the tissue density maps are input to the algorithm, variances become even further reduced though the mean deviations are less affected. The newly proposed hybrid DNN-EMD method for individualized radiation dose prediction outperforms the MIRD DVK dose calculation method. It is fast enough to be of use in daily clinical practice.

A comparison of methods for adapting [Formula: see text] dose-voxel-kernels to tissue inhomogeneities.

In [Formula: see text] radionuclide therapies, dosimetry is used for determining patient-individual dose burden. Standard approaches provide whole organ doses only. For assessing dose heterogeneity inside organs, voxel-wise dosimetry based on 3D SPECT/CT imaging could be applied. Often, this is achieved by convolving voxel-wise time-activity-curves with appropriate dose-voxel-kernels (DVK). The DVKs are meant to model dose deposition, and can be more accurate if modelled for the specific tissue type under consideration. In literature, DVKs are often not adapted to these inhomogeneities, or simple approximation schemes are applied. For 26 patients, which had previously undergone a [Formula: see text] -PSMA or -DOTATOC therapy, decay maps, mass-density maps as well as tissue-type maps were derived from SPECT/CT acquisitions. These were used for a voxel-based dosimetry based on convolution with DVKs (each of size [Formula: see text]) obtained by four different DVK methods proposed in literature. The simplest only considers a spatially constant soft-tissue DVK (herein named 'constant'), while others either take into account only the local density of the center voxel of the DVK (herein named 'center-voxel') or scale each voxel linearly according to the proper mass density deduced from the CT image (herein named 'density') or considered both the local mass density as well as the direct path between the center voxel and any voxel in its surrounding (herein named 'percentage'). Deviations between resulting dose values and those from full Monte-Carlo simulations (MC simulations) were compared for selected organs and tissue-types. For each DVK method, inter-patient variability was considerable showing both under- and over-estimation of energy dose compared to the MC result for all tissue densities higher than soft tissue. In kidneys and spleen, 'constant' and 'density'-scaled DVKs achieved estimated doses with smallest deviations to the full MC gold standard (∼[Formula: see text] underestimation). For low and high density tissue types such as lung and adipose or bone tissue, alternative DVK methods like 'center-voxel'- and 'percentage'- scaled achieved superior results, respectively. Concerning computational load, dose estimation with the DVK method 'constant' needs about 1.1 s per patient, center-voxel scaling amounts to 1.2 s, density scaling needs 1.4 s while percentage scaling consumes 860.3 s per patient. In this study encompassing a large patient cohort and four different DVK estimation methods, no single DVK-adaption method was consistently better than any other in case of soft tissue kernels. Hence in such cases the simplest DVK method, labeled 'constant', suffices. In case of tumors, often located in tissues of low (lung) or high (bone) density, more sophisticated DVK methods excel. The high inter-patient variability indicates that for evaluating new algorithms, a sufficiently large patient cohort needs to be involved.

Two decades of SPECT/CT - the coming of age of a technology: An updated review of literature evidence.

PURPOSE: Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) was introduced as a hybrid SPECT/CT imaging modality two decades ago. The main advantage of SPECT/CT is the increased specificity achieved through a more precise localization and characterization of functional findings. The improved diagnostic accuracy is also associated with greater diagnostic confidence and better inter-specialty communication. METHODS: This review presents a critical assessment of the relevant literature published so far on the role of SPECT/CT in a variety of clinical conditions. It also includes an update on the established evidence demonstrating both the advantages and limitations of this modality. CONCLUSIONS: For the majority of applications, SPECT/CT should be a routine imaging technique, fully integrated into the clinical decision-making process, including oncology, endocrinology, orthopaedics, paediatrics, and cardiology. Large-scale prospective studies are lacking, however, on the use of SPECT/CT in certain clinical domains such as neurology and lung disorders. The review also presents data on the complementary role of SPECT/CT with other imaging modalities and a comparative analysis, where available.

Factors affecting accuracy of S values and determination of time-integrated activity in clinical Lu-177 dosimetry.

INTRODUCTION: In any radiotherapy, the absorbed dose needs to be estimated based on two factors, the time-integrated activity of the administered radiopharmaceutical and the patient-specific dose kernel. In this study, we consider the uncertainty with which such absorbed dose estimation can be achieved in a clinical environment. METHODS: To calculate the total error of dose estimation we considered the following aspects: The error resulting from computing the time-integrated activity, the difference between the S-value and the patient specific full Monte Carlo simulation, the error from segmenting the volume-of-interest (kidney) and the intrinsic error of the activimeter. RESULTS: The total relative error in dose estimation can amount to 25.0% and is composed of the error of the time-integrated activity 17.1%, the error of the S-value 16.7%, the segmentation error 5.4% and the activimeter accuracy 5.0%. CONCLUSION: Errors from estimating the time-integrated activity and approximations applied to dose kernel computations contribute about equally and represent the dominant contributions far exceeding the contributions from VOI segmentation and activimeter accuracy.

ROC study and SUV threshold using quantitative multi-modal SPECT for bone imaging.

BACKGROUND: We investigated the clinical performance of a quantitative multi-modal SPECT/CT reconstruction platform for yielding radioactivity concentrations of bone imaging with 99mTc-methylene diphosphonate (MDP) or 99mTc-dicarboxypropane diphosphonate (DPD). The novel reconstruction incorporates CT-derived tissue information while preserving the delineation of tissue boundaries. We assessed image-based reader concordance and confidence, and determined lesion classification and SUV thresholds from ROC analysis. METHODS: Seventy-two cancer patients were scanned at three US and two German clinical sites, each contributing two experienced board-certified nuclear medicine physicians as readers. We compared four variants of the reconstructed data resulting from the Flash3D (F3D) and the xSPECT Bone™ (xB) iterative reconstruction methods and presented images to the readers with and without a fused CT, resulting in four combinations. We used an all-or-none approach for inclusion, compiling results only when a reader completed all reads in a subset. After the final read, we conducted a "surrogate truth" reading, presenting all data to each reader. For any remaining discordant lesions, we conducted a consensus read. We next undertook ROC analysis to determine SUV thresholds for differentiating benign and lesional uptake. RESULTS: On a five-point rating scale of image quality, xB was deemed better by almost two points in resolution and one point better in overall acceptance compared to F3D. The absolute agreement of the rendered decision between the nine readers was significantly higher with CT information either inside the reconstruction (xB, xBCT) or simply through image fusion (F3DCT): 0.70 (xBCT), 0.67 (F3DCT), 0.64 (xB), and 0.46 (F3D). The confidence level to characterize the lesion was significantly higher (3.03x w/o CT, 1.32x w/CT) for xB than for F3D. There was high correlation between xB and F3D scores for lesion detection and classification, but lesion detection confidence was 41% higher w/o CT, and 21% higher w/CT for xB compared to F3D. Without CT, xB had 6.6% higher sensitivity, 7.1% higher specificity, and 6.9% greater AUC compared to F3D, and similarly with CT-fusion. The overall SUV-criterion (SUVc) of xB (12) exceeded that for xSPECT Quant™ (xQ; 9), an approach not using the tissue delineation of xB. SUV critical numbers depended on lesion volume and location. For non-joint lesions > 6 ml, the AUC for xQ and xB was 94%, with SUVc > 9.28 (xQ) or > 9.68 (xB); for non-joint lesions ≤ 6 ml, AUCs were 81% (xQ) and 88% (xB), and SUVc > 8.2 (xQ) or > 9.1 (xB). For joint lesions, the AUC was 80% (xQ) and 83% (xB), with SUVc > 8.61 (xQ) or > 13.4 (xB). CONCLUSION: The incorporation of high-resolution CT-based tissue delineation in SPECT reconstruction (xSPECT Bone) provides better resolution and detects smaller lesions (6 ml), and the CT component facilitates lesion characterization. Our approach increases confidence, concordance, and accuracy for readers with a wide range of experience. The xB method retained high reading accuracy, despite the unfamiliar image presentation, having greatest impact for smaller lesions, and better localization of foci relative to bone anatomy. The quantitative assessment yielded an SUV-threshold for sensitively distinguishing benign and malignant lesions. Ongoing efforts shall establish clinically usable protocols and SUV thresholds for decision-making based on quantitative SPECT.

[Somatostatin receptor PET/CT (SSTR-PET/CT)]. / Somatostatinrezeptor-PET/CT.

The present guideline is focused on quality assurance of somatostatin receptor PET/CT (SSTR-PET/CT) in oncology patients. The document has been developed by a multidisciplinary board of specialists providing consensus of definitions, prerequisites, methodology, operating procedures, assessment, and standardized reporting. In particular, imaging procedures for the two most commonly used radioligands of human SSTR, i. e. 68Ga-DOTATOC and 68Ga-DOTATATE are presented. Overall, SSTR-PET/CT requires close interdisciplinary communication and cooperation of referring and executing medical disciplines, taking into account existing guidelines and recommendations of the European and German medical societies, including the European Association of Nuclear Medicine (EANM), German Society for Endocrinology (DGE), German Society for Nuclear Medicine (DGN) and German Society for Radiology (DRG).

The EANM practice guidelines for bone scintigraphy.

PURPOSE: The radionuclide bone scan is the cornerstone of skeletal nuclear medicine imaging. Bone scintigraphy is a highly sensitive diagnostic nuclear medicine imaging technique that uses a radiotracer to evaluate the distribution of active bone formation in the skeleton related to malignant and benign disease, as well as physiological processes. METHODS: The European Association of Nuclear Medicine (EANM) has written and approved these guidelines to promote the use of nuclear medicine procedures of high quality. CONCLUSION: The present guidelines offer assistance to nuclear medicine practitioners in optimizing the diagnostic procedure and interpreting bone scintigraphy. These guidelines describe the protocols that are currently accepted and used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.

Thoracic non-osseous lesions in cancer patients detected in low-dose CT images acquired as part of skeletal SPECT/CT examinations.

AIM: Hybrid single-photon emission tomographic (SPECT) and X-ray computed tomography (CT) systems are increasingly used in oncologic imaging. With SPECT/CT not only the thoracic spine but also the surrounding soft tissue needs to be evaluated for pathological findings. The purpose of this study was to assess the prevalence of non-osseous findings detectable on low-dose CT datasets from patients studied by thoracic 99mTc-dicarboxypropane diphosphonate (DPD)-SPECT/CT. PATIENTS, METHODS: 119 consecutive oncologic patients (81 breast cancer, 38 with other cancer) who underwent DPD-SPECT CT of the thoracic region were included in this study. Non-osseous findings on CT were classified as either probably benign or suspicious. Suspicious findings were correlated with retrievable previous imaging and if performed with follow up imaging (MRI, CT with contrast medium, Ultrasound) or biopsy results. RESULTS: In 80/119 (67%) patients no imaging was performed before SPECT/CT. Only 7/119 subjects (6%) had no other lesions than bone lesions. In 101/119 (85%) patients lesions found on SPECT/CT images were rated as benign and in 65/119 (55%) patients as suspicious. In 8/119 (7%) patients with previously unknown suspicious lesions on SPECT/CT images suspicious findings were confirmed by biopsy. CONCLUSION: 7% of patients referred to SPECT/CT of the thoracic spine for staging of malignant disease had previously unknown suspicious non-osseous lesions detectable on the low-dose CT images which were confirmed by biopsy. This could be especially relevant for cancer entities like breast and prostate, in which no thorax-CT is routinely intended for staging.

Quantitative SPECT/CT Imaging of (177)Lu with In Vivo Validation in Patients Undergoing Peptide Receptor Radionuclide Therapy.

PURPOSE: The purpose of this study is to extend an established SPECT/CT quantitation protocol to (177)Lu and validate it in vivo using urine samples, thus providing a basis for 3D dosimetry of (177)Lu radiotherapy and improvement over current planar methods which improperly account for anatomical variations, attenuation, and overlapping organs. PROCEDURES: In our quantitation protocol, counts in images reconstructed using an ordered subset-expectation maximization algorithm are converted to kilobecquerels per milliliter using a calibration factor derived from a phantom experiment. While varying reconstruction parameters, we tracked the ratio of image to true activity concentration (recovery coefficient, RC) in hot spheres and a noise measure in a homogeneous region. The optimal parameter set was selected as the point where recovery in the largest three spheres (16, 8, and 4 ml) stagnated, while the noise continued to increase. Urine samples were collected following 12 SPECT/CT acquisitions of patients undergoing [(177)Lu]DOTATATE therapy, and activity concentrations were measured in a well counter. Data was reconstructed using parameters chosen in the phantom experiment, and estimated activity concentration from the images was compared to the urine values to derive RCs. RESULTS: In phantom data, our chosen parameter set yielded RCs in 16, 8, and 4 ml spheres of 80.0, 74.1, and 64.5 %, respectively. For patients, the mean bladder RC was 96.1 ± 13.2% (range, 80.6-122.4 %), with a 95 % confidence interval between 88.6 and 103.6 %. The mean error of SPECT/CT concentrations was 10.1 ± 8.3% (range, -19.4-22.4 %). CONCLUSIONS: Our results show that quantitative (177)Lu SPECT/CT in vivo is feasible but could benefit from improved reconstruction methods. Quantifying bladder activity is analogous to determining the amount of activity in the kidneys, an important task in dosimetry, and our results provide a useful benchmark for future efforts.

Metastases of non-thyroidal tumors to the thyroid gland: a regional survey in middle franconia.

OBJECTIVE: Metastases of non-thyroidal tumors to the thyroid gland are infrequently diagnosed in the clinical environment. In autopsy studies, however, metastases to the thyroid gland have a frequency of 1.25-24%. The aim of this investigation was to explore the primary tumor and latency of diagnosis in patients who were diagnosed with metastases to the thyroid gland in 70 institutions associated to a scientific board in Middle Franconia during a 12 year period. DESIGN: Retrospective cross-sectional study. PATIENTS: After a clinical data base research, 35 patients (21 male, 14 female) with a histological diagnosis of a secondary thyroid malignancy were identified between 2002 and 2013. The mean age of the patients at diagnosis of the metastasis was x=68.2 years (median: 70, standard deviation SD=± 8.4, range 46-85 years). The majority of the patients had metastases from renal cell carcinomas (n=19). In the other patients metastases from gastrointestinal carcinomas (n=2), bronchial carcinomas (n=3), malignant melanomas (n=3), sarcomas (n=2), and other tumors (n=6) were diagnosed. The time interval between the diagnosis of the primary tumor and the metastasis to the thyroid gland was different for patients with metastases from renal cell carcinomas and non-renal cell carcinomas (p<0.001, chi-test). CONCLUSIONS: In agreement with previous studies, the majority of metastases to the thyroid gland derive from renal cell carcinomas. In patients with non-renal malignancies, metastases to the thyroid gland are diagnosed simultaneously with the primary tumor to a higher proportion compared with metastasis from renal malignancies.

Differential diagnostic ultrasound criteria of papillary and follicular carcinomas: a multivariate analysis.

PURPOSE: The purpose of the study was to test the hypothesis that papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs) appear with different ultrasound characteristics. MATERIAL AND METHODS: 90 patients (70 females, 20 males) were included in the study in whom after thyroidectomy the diagnoses of PTCs or FTCs were established. 33 patients (25 females, 8 males) with the diagnosis of follicular adenoma were included in the study as controls (KONs). All patients had ultrasound examinations of the thyroid preoperatively. These ultrasound examinations were evaluated retrospectively with respect to the ultrasound characteristics: "size", "shape", "contour", "structure", "echogenicity" and "calcifications". RESULTS: In PTCs, FTCs and KONs "size" was significantly different (PTCs: MW = 12.5 mm, SD = 8.  mm - FTCs: MW = 35.4 mm, SD = 19.6  mm - KONs: MW = 22.7 mm, SD = 14.5  mm; p <  0.001 for PTCs vs. FTCs, p < 0.001 for PTCs vs. KONs, p = 0.013 for FTCs vs. KONs). Differences were also found with respect to "contour" and "echogenicity" among PTCs, FTCs and KONs (p ≤ 0.035). The parameters "size", "contour", "echogenicity" and "calcifications" correlated for PTCs, FTCs and KONs with a correlation coefficient r = 0.57 (p < 0.05, multivariate regressionanalysis). CONCLUSIONS: PTCs and FTCs appear with different sonographic characteristics. Although there is some overlapping of the sonographic appearances of PTCs and FTCs, the knowledge of these differences should have some impact of the risk adapted further work up.

Interictal magnetoencephalography used in magnetic resonance imaging-negative patients with epilepsy.

PURPOSE: This study aims to investigate the contributions of magnetoencephalography (MEG) in magnetic resonance imaging (MRI)-negative patients. METHODS: A total of 18 MRI-negative patients diagnosed with refractory epilepsy, subjected to MEG investigation, and subsequently underwent surgery were selected for retrospective analysis. A 1.5-tesla Magnetom Sonata with an eight-channel head array coil was used. MEG data were obtained using a 74/248-channel system. RESULTS: A total of 16 patients (16/18) had positive MEG results, comprising 12 patients with monofocal localizations, five with multifocal localizations, and one with unremarkable results in MEG. In addition, 12 patients had indicative single photon-emission computed tomography (SPECT), five had indicative fluorodeoxyglucose positron emission tomography (FDG-PET), and all the patients had intracranial electroencephalography (EEG) (14 with subdural electrodes and four with electrocorticography). The intracranial EEG recordings of nine patients were guided by MEG informative results. Among these 18 patients, 10 exhibited good postoperative outcomes (Engel I and II), four of which were completely seizure-free. All these ten patients had clear monofocal localization in MEG, including nine with accordant indicative metabolic changes in either SPECT or FDG-PET, or both. None of the five patients with multifocal localizations achieved good postoperative outcomes. CONCLUSION: For cases with negative MRI findings, epilepsy surgery may be an alternative option for pharmaco-resistant patients if epileptogenic focus localizations by MEG are present in multimodal evaluation.

Diagnostic value and therapeutic impact of (18)F-FDG-PET/CT in differentiated thyroid cancer. Results of a German multicentre study.

UNLABELLED: The clinical significance of (18)F-FDG-PET/CT in the follow-up of patients with differentiated thyroid carcinoma was evaluated and the results were compared with those of (18)F-FDG-PET, (131)I-whole-body scintigraphy including SPECT/CT (WBS) and ultrasound. In addition, it was the aim to investigate the impact of (18)F-FDG-PET/CT on the therapeutic management. PATIENTS, METHODS: 327 patients (209 women, 118 men; mean age 53 ± 18 years) with differentiated thyroid cancer (242 papillary, 75 follicular, 6 mixed, 1 Hürthle cell and 3 poorly differentiated tumours) were analyzed retrospectively at four tertiary referral centres. 289 (18)F-FDG-PET/CT and 118 (18)F-FDG-PET studies were performed in these patients between 2007 and 2010. In addition, an overall clinical evaluation was performed, including cytology, histology, thyroglobulin level, ultrasound, WBS, and subsequent clinical course in order to compare the molecular imaging results. Finally, the change in therapeutic management due to findings of (18)F-FDG-PET/CT was investigated. RESULTS: The sensitivity of (18)F-FDG-PET/CT was 92%, the specificity was 95%. Sensitivity and specificity of (18)F-FDG-PET alone were 67% and 93%, respectively. WBS showed a sensitivity of 65% and a specificity of 94%. The corresponding values of ultrasound were 37% and 94%, respectively. The sensitivity of (18)F-FDG-PET/CT in the group of patients with a negative WBS (n=194) amounted to 96%. When (18)F-FDG-PET/CT and WBS were considered in combination, tumour tissue was missed in only 2 out of 133 patients; when (18)F-FDG-PET and WBS were combined, tumour tissue was missed in 1 out of 24 patients. (18)F-FDG-PET/CT resulted in management change in 43% (n=57/133) with a decision on surgical approach in 20% (n=27/133). CONCLUSIONS: (18)F-FDG-PET/CT is superior to (18)F-FDG-PET alone in patients with differentiated thyroid cancer and has a direct impact on the therapeutic management of patients with suspected local recurrence or metastases, particularly in those with negative WBS.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

Anatomical accuracy of abdominal lesion localization. Retrospective automatic rigid image registration between FDG-PET and MRI.

UNLABELLED: Software-based image registration can improve the diagnostic value of imaging procedures and is an alternative to hybrid scanners. The aim of this study was to evaluate the anatomical accuracy of automatic rigid image registration of independently acquired datasets of positron emission tomography with 18F-deoxyglucose and abdominal magnetic resonance imaging. PATIENTS, METHODS: Analyses were performed on 28 abdominal lesions from 20 patients. The PET data were obtained using a stand-alone PET camera in 14 cases and a hybrid PET/CT scanner in 9 cases. The abdominal T1- and T2-weighted MRI scans were acquired on 1.5 T MRI scanners. The mean time interval between MRI and PET was 7.3 days (0-28 days). Automatic rigid registration was carried out using a self-developed registration tool integrated into commercial available software (InSpace for Siemens Syngo). Distances between the centres of gravity of 28 manually delineated neoplastic lesions represented in PET and MRI were measured in X-, Y-, and Z-direction. The intra- (intraclass correlation 0.94) and inter- (intraclass correlation 0.86) observer repeatability were high. RESULTS: The average distance in all MRI sequences was 5.2±7.6 mm in X-direction, 4.0±3.7 mm in Y-direction and 6.1±5.1 mm in Z-direction. There was a significantly higher misalignment in Z-direction (p<0.05). The misalignment was not significantly different for the registration of T1- and T2- weighted sequences (p=0.7). CONCLUSION: The misalignment between FDG-PET and abdominal MRI registered using an automated rigid registration tool was comparable to data reported for software-based fusion between PET and CT. Although this imprecision may not affect diagnostic accuracy, it is not sufficient to allow for pixel-wise integration of MRI and PET information.

[Sensitivity of neurochemical dementia diagnostics in CSF compared to 99mTc-SPECT in Alzheimer's dementia]. / Vergleichende Sensitivität der neurochemischen Demenzdiagnostik im Liquor und rCBF im 99mTc-SPECT bei Patienten mit Alzheimerdemenz.

The diagnosis of Alzheimer's dementia is currently changing from a late and exclusion diagnosis towards a pathophysiology-based early and positive diagnosis. Especially advances in neuro-chemical dementia diagnostics in the cerebrospinal fluid (NDD-CSF) and imaging techniques like PET, SPECT or MRI are of particular interest. Unfortunately, many studies investigated only either one or other technique. In the present study 56 patients (average 67.1 years; average mini-mental status test (MMST) 22.2) were examined with the clinical diagnosis of Alzheimer's dementia. All patients both underwent NDD-CSF as well as 99mTc-SPECT. Only the SPECT, but not the NDD-CSF correlated with disease severity. Sensitivity of NDD-CSF was 89 % and SPECT 48 % for all patients and 93 % resp. 61 % for patients with MMST < 24. Below MMST 20 both methods had equal sensitivity. Both diagnostic techniques showed no statistic coherence (p = 0.27), neither after correction for subgroups like disease severity or the APOE genotype. Our results are compatible with the hypothesis that the NDD-CSF reflects beta-amyloid-aggregation and Tau-Protein pathology as a pathophysiologic biomarker. Our results suggest that SPECT is rather a state parameter for the rCBF changes following cortical neurodegeneration.

Specific accumulation of 18F-deoxyglucose in three-dimensional long-term cultures of human and rodent brain tissue.

AIM: Organotypic slice cultures (OSC) of human brain specimens represent an intriguing experimental model for translational studies addressing, e.g., stem cell transplantation in neurodegenerative diseases or targeting invasion by malignant glioma ex vivo. However, long-term viability and phenomena of structural reorganization of human OSC remain to be further characterized. Here, we report the use of (18)F-deoxyglucose (FDG) for evaluating the viability of brain slice preparations obtained either from postnatal rats or human hippocampal specimens. METHODS: Anatomically well preserved human hippocampi obtained from epilepsy surgery and rat hippocampus slice cultures obtained from six day old Wistar rats were dissected into horizontal slices. The slices were incubated with FDG in phosphate buffered saline up to 1 h, either with or without supplementation of glucose at a concentration of 2.5 mg/ml. Radioactivity within the medium or slice cultures was measured using a gamma-counter. In addition, distribution of radioactivity was autoradiographically visualized and quantified as counts per mm(2). RESULTS: In rat hippocampal slices, FDG accumulated with 1 300 000 +/- 68 000 counts/mm(2), whereas the incorporation of the radioactive label in human slices was in the order of 1 500 000 +/- 370 000 counts/mm(2). The elevation of glucose concentration within the medium led to a significant three-fold decrease of FDG accumulation in rat slices and to a 2.4-fold decrease in human specimens. CONCLUSIONS: FDG accumulated in organotypic brain cultures of human or rodent origin. FDG is thus suited to investigate the viability of OSC. Furthermore, these preparations open new ways to study the factors governing cerebral FDG uptake in brain tissue ex vivo.

Multimodal coregistration in patients with temporal lobe epilepsy--results of different imaging modalities in lateralization of the affected hemisphere in MR imaging positive and negative subgroups.

BACKGROUND AND PURPOSE: In this study, intensive video electroencephalogram (EEG) monitoring, high-resolution MR imaging (MR imaging), proton MR spectroscopy ((1)H-MR spectroscopy) and single-photon emission CT (SPECT) were compared in patients with temporal lobe epilepsy (TLE) to evaluate lateralization of affected hemisphere with regard to bilateral affection and postoperative outcome. PATIENTS AND METHODS: Recall ratio of each technique for indicating the affected hemisphere was determined in 49 patients with TLE. Postoperative outcome was established by Engel classification. RESULTS: Twenty-two of 25 patients with TLE with evidence for hippocampal sclerosis in MR imaging (MR imaging-positive) were graded as unilateral by EEG findings whereas 3 were classified as bilateral. Fourteen of 24 MR imaging-negative patients were graded as unilateral by EEG and 10 as bitemporal. (1)H-MR spectroscopy indicated concordant lateralization to EEG in 82% of MR imaging-positive patients and 71% of MR imaging-negative patients and to SPECT in 84% of MR imaging-positive patients and 67% of MR imaging-negative patients with TLE. In unilateral TLE, the concordance rate of both modalities was 74% in MR imaging-positive patients and 67% in MR imaging-negative patients. Contralateral findings to EEG focus were found in 28% by (1)H-MR spectroscopy and in 27% by SPECT. Concordant findings to the operated side of different modalities revealed a clear tendency (P = .08) for a better postoperative outcome compared with bitemporal or contralateral findings. CONCLUSION: Our data demonstrate that multimodal imaging in patients with TLE improves lateralization of affected hemispheres, especially in patients without pathologic findings in MR imaging, and indicates bilateral effect, which is important to identify patients who will benefit from surgery.